Project Summary This year cancer is expected to claim 8.8 million lives worldwide (World Health Organization). It represents the leading cause of death in the United States and its prevalence continues to grow each year. Conventional treatment options tend to be limited in efficacy with highly toxic side effects. Newer, monoclonal antibody-based therapies have offered promise to for some types of cancer, particularly blood tumors, but these often fall short as well. Typically, these treatments are delivered based on the location of the tumor and do not consider whether the individual patient actually expresses the target. In addition, the most common tumor antigens tend to have significant expression on healthy tissues as well, creating ?on-target, off-tumor? toxicities. Recent advances in nucleotide sequencing technology have created a proliferation in precision oncology capabilities. These new capabilities have allowed patients and their tumors to be stratified, knowing exactly which patients? tumors express druggable targets. These advances have created a gap in the field between the ability to identify unique tumor markers and the ability deliver therapies based on those markers. The maturation of precision oncology establishes an urgent need for development of therapeutics to novel targets intended to treat cancers based on their genetic composition rather than their location. Using proprietary computational biology techniques, we have populated a list of antigens that are very highly expressed on small subsets (2-10%) of tumors but are not expressed or have very low expression on healthy tissues. With this Phase I SBIR, we hope to advance our first therapeutics to one of these targets through pre-clinical proof-of-concept experiments and lead candidate selection. These experiments will drive the selection of the optimal format of this therapeutic and will justify the IND-enabling pre-clinical work required to prepare these novel therapeutics for delivery to patients.